DIFFERENTIAL COMPARTMENTALIZATION OF BRAIN ASCORBATE AND GLUTATHIONE BETWEEN NEURONS AND GLIA

Compartmentalization of brain ascorbate and glutathione between neuron s and glia has been a source of controversy. To address this question, we determined the ascorbate and glutathione contents of brain tissue with defined, but varying, densities of neurons and glia. In developin g rat cortex and hippocampus, glutathione content rose during gliogene sis, while ascorbate fell. By contrast, ascorbate, but not glutathione , increased markedly during granule cell proliferation and maturation in the developing cerebellum. Similarly, in tissue from adult cerebral cortex of species with distinct neuron densities, ascorbate content i ncreased linearly with increasing neuron density in the order: human < rabbit < guinea-pig < rat < mouse, whereas glutathione was relatively constant. These data suggest that ascorbate predominates in neurons, whereas glutathione is slightly predominant in glia. Quantitative anal ysis of ascorbate and glutathione contents in these studies combined w ith appropriate intra-and extracellular volume fraction data permitted calculation of concentrations of ascorbate in neurons (10 mM) and gli a (0.9 mM), and glutathione in neurons (2.5 mM) and glia (3.8 mM). The relative accuracy of these values was confirmed by their use in a mod el that reliably predicted changes in ascorbate and glutathione levels in rat cortex during the first three postnatal weeks and into adultho od. These finding not only provide new information about the intracell ular composition of neurons and glia, but also have implications for u nderstanding the roles of ascorbate and glutathione in normal brain fu nction, as well as neuron and glia involvement in disease states linke d to oxidative stress. (C) 1997 IBRO. Published by Elsevier Science Lt d.